Both 2-chloro-11-(piperazinyl)-dibenz[b,f][1,4]oxazepine and 2-chloro-11-(4-methyl-1-piperazinyl)-dibenz[b,f][1,4]oxazepine are known compounds having therapeutic effects on the central nervous system.
U.S. Pat. No. 3,546,226 specifically discloses the compound 2-chloro-11-(4-methyl-1-piperazinyl)-dibenz[b,f][1,4]oxazepine, and broadly discloses the compound 2-chloro-11-(piperazinyl)-dibenz[ b,f][1,4]oxazepine, their method of preparation, their non-toxic pharmaceutically acceptable acid addition salts and their utility as central nervous system agents. The '226 patent also discloses the parenteral administration of the above compounds. However, the '226 patent does not disclose sustained release forms of the above compounds as set forth herein.
U.S. Pat. No. 3,663,696 discloses the preparation and treatment of depression with 2-chloro-11-(1-piperazinyl)-dibenz[b,f][1,4]oxazepines and the acid addition salts thereof, including the hydrochloride, sulfate, phosphate, citrate, tartrate, maleate, succinate and fumarate. The '696 patent also discloses parenteral administration of the above compounds, and a specific parenteral solution of 2-chloro-11-(1-piperazinyl)-dibenz[b,f][1,4]oxazepine. However, the '696 patent does not disclose sustained release forms of the above compounds as set forth herein.
U.S. Pat. No. 3,194,733 discloses certain acid esters of phenothiazines useful as tranquilizing or ataractic agents such as the enanthate ester of fluphenazine. The '733 patent discloses the pamoate ester and parenteral formations comprising phenothiazine compounds and aluminum monostearate in vegetable oils or synthetic esters of long chain fatty acids. However, the pamoate of the present invention is not a phenothiazine or an acid ester, but the salt of a base, and is structurally different from the acid ester compounds disclosed in the '733 patent.
Prior to the present invention, there was no prolonged acting central nervous system formulation of 2-chloro-11-(1-piperazinyl)-dibenz[b,f][1,4]oxazepine or 2-chloro-11-(4-methyl-1-piperazinyl)-dibenz[b,f][1,4]oxazepine, in either the free base or pamoate salt forms. The present invention supplies such formulations. Formulations, capable of prolonged action and consequently less frequent administration, are much desired as they are more convenient and easier to use where continuous and uninterrupted administration is needed.